The Effect of Pioglitazone and Metformin on Liver Function Tests, Insulin Resistance, and Liver Fat Content in Nonalcoholic Fatty Liver Disease: A Randomized Double Blinded Clinical Trial

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of insulin resistance (IR) syndrome. The effect of insulin sensitizers on liver function tests and metabolic indices in NAFLD patients is a matter of debate.ObjectivesThe aim of study was to compare the effects of two different insulin sensitizers, pioglitazone, and metformin, on liver function tests (LFT), lipid profile, homeostasis model assessment-IR (HOMA-IR) index, and liver fat content (LFC) in NAFLD patients.Materials and MethodsThis double blind clinical trial was performed on patients who were referred to a gastroenterology clinic with evidence of fatty liver in ultrasonography. After excluding other causes, participants with persistent elevated alanine aminotransferase (ALT) levels and “NAFLD liver fat score” greater than -0.64 were presumed to have NAFLD and were enrolled. They were randomly assigned to take metformin (1 g/day) or pioglitazone (30 mg/day) for four months. Fasting serum glucose (FSG), ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, cholesterol (CHOL), high and low density lipoprotein (HDL, LDL), HOMA-IR, and LFC were checked at the baseline, two and four months post-treatment. LFC was measured by a validated formula.ResultsEighty patients (68 males) with mean age of 35.27 (± 7.98) were included. After 2 months, LFT was improved significantly in the pioglitazone group and did not change in the metformin group. After four months, both medications significantly decreased serum levels of LFT, FSG, CHOL, LDL, HOMA-IR, and LFC, and increased serum level of HDL. No statistically significant differences were seen between the two treatment groups with regard to the changes of laboratory parameters and LFC from baseline to four months post-treatment.ConclusionsDuring the four months, the use of metformin (1 g/day) and pioglitazone (30 mg/day) were safe and might have equally affected LFT, HOMA-IR, lipid profile, and LFC in NAFLD patients.

Pioglitazone versus metformin in Egyptian non diabetic patients with Non Alcholic Fatty Liver Disease: A randomized controlled trial.

“…These findings were in accordance with the results of previous trials that illustrated that serum TG level did not change significantly following pioglitazone treatment [7] or metformin treatment [25] in NAFLD patients. As observed by our data, the post treatment level of LDL-C decreased significantly in metformin group but not in pioglitazone group.…”

“…These results were in accordance with Razavizade et al [7], who revealed a significant decrease in liver fat content in NAFLD patients treated with either metformin or pioglitazone. The study of Belfort et al [24] measured liver fat content by magnetic resonance spectroscopy, which showed a significant reduction by 54% in pioglitazone treated NAFLD patients.…”

“…Our data were in accordance with previous reports. Razavizade et al [7] revealed that four-months of treatment of NAFLD patients with metformin (1g/day) or pioglitazone (30 mg/day) led to a significant decrease in HOMA-IR in both groups. Bugianesi et al [23] reported that metformin (2 g/day) was effective in decreasing insulin level in fifty-five NAFLD patients for twelve-months.…”

“…Pioglitazone, a thiazolidinedione derivative, is a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist that improves insulin sensitivity and glucose and lipid metabolism in type II diabetes [6]. Treatment with thiazolidinediones results in consistent decrease in Free Fatty Acids (FFAs) [7], thereby decreasing FFA delivery to the liver. They also increase adiponectin levels which may help to increase lipid oxidation of fatty acids in the liver [6].…”

Fatty Liver Index (FLI) in Predicting Non-alcoholic Fatty Liver Disease (NAFLD)

“…Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis defined as accumulation of fat in the liver tissue in the absence of any secondary cause, such as excess consumption of alcohol or drugs that can lead to cirrhosis and hepatocellular carcinoma (1,2). Nonalcoholic fatty liver disease has a range of clinical conditions encompassing simple steatosis (fatty accumulation in the liver tissue), non-alcoholic steatohepatitis (NASH) (inflammatory cell infiltration in the liver), hepatocyte ballooning, and hepatic cirrhosis (3).…”